Memory-like Natural Killer (NK) Cell Therapy in Patients With Renal Cell Carcinoma or Urothelial Carcinoma (NCT06318871)

Usually NOT eligible if any of the following apply:

• Exclusion Criteria:
• Participants who have had anti-tumor chemotherapy or other investigational agents within 2 weeks prior to enrollment(4 weeks for nitrosoureas or mitomycin C), or immunotherapy within 4 weeks prior.
• Persisting toxicity related to prior therapy (NCI CTCAE Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• Prior recipients of solid organ transplantation.
• Participants who are receiving any other investigational agents.
• Participants with leptomeningeal disease are excluded from this clinical trial due to their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated brain metastases are eligible if imaging has shown stability over at least 4 weeks.
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, are excluded from this study, as are patients with a history of active autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[Wegener's granulomatosis\]) and motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis). Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or unstable cardiac arrhythmia requiring medication. Patients with rate controlled atrial fibrillation / atrial flutter on stable medical therapy are eligible.
• Other uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, or uncontrolled psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or other psychiatric illness/social situations that would limit compliance with study requirements, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Participants with known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of enrollment, with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy, or cancers from which the patient has been disease-free for \> 1 year after treatment with curative intent.
• No systemic corticosteroid therapy (≥ 10 mg of prednisone or equivalent dose of systemic steroids for non-autoimmune indications for at least 2 weeks prior to enrollment).
• Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and IL-2 and with the potential for teratogenic or abortifacient effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and IL-2, breastfeeding should be discontinued if the mother is treated on this study. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study or 12 months after last treatment, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 months after completion of the last CIML NK cell and/or last IL-2 administration.